Real-World Effectiveness and Safety of Glecaprevir/Pibrentasvir for the Treatment of Chronic Hepatitis C: A Prospective Cohort Study in Portugal.

INTRODUCTION: Information about pan-genotypic treatments for hepatitis in Portugal is scarce. We aimed to evaluate the effectiveness and safety of glecaprevir plus pibrentasvir (GLE/PIB) treatment for hepatitis C virus (HCV) infection in real-world clinical practice. METHODS: An observational prospective study was implemented in six hospitals with 121 adult HCV patients who initiated treatment with GLE/PIB between October 2018 and April 2019, according to clinical practice. Eligible patients had confirmed HCV infection genotype (GT) 1 to 6 and were either treatment-naïve or had experience with interferon-, ribavirin- or sofosbuvir-based regimens, with or without compensated cirrhosis. Baseline sociodemographic and safety data are described for the total population (N = 115). Effectiveness [sustained virologic response 12 weeks after treatment (SVR12)] and patient-reported outcomes are presented for the core population with sufficient follow-up data (n = 97). RESULTS: Most patients were male (83.5%), aged < 65 years (94.8%), with current or former alcohol consumption (77.3%), illicit drug use (72.6%), and HCV acquisition through intravenous drug use (62.0%). HIV co-infection occurred in 22.6% of patients. The prevalence of each GT was: GT1 51.3%, GT2 1.7%, GT3 30.4%, GT4 16.5%, and GT5.6 0%. Most patients were non-cirrhotic (80.9%) and treatment-naïve (93.8%). The SVR12 rates were 97.9% (95% CI: 92.8 - 99.4), and > 95% across cirrhosis status, GT, illicit drug use, alcohol consumption, and HCV treatment experience. The adverse event rate was 2.6%, and no patient discontinued treatment due to adverse events related to GLE/PIB. CONCLUSION: Consistent with other real-world studies and clinical trials, treatment with GLE/PIB showed high effectiveness and tolerability overall and in difficult-to-treat subgroups (ClinicalTrials.gov: NCT03303599).

A Rare Cause of Abdominal Pain: IgG4-Related Sclerosing Mesenteritis.

A 67-year-old man with previous cardiovascular disease was referred to our consultation due to a 5-month history of recurrent epigastric pain. Esophagogastroduodenoscopy and full blood workup presented no alterations. CT scan showed an irregularly shaped mass at the root of the mesentery, measuring 40x25x47mm, with spiculated contours and retractile behaviour (a). Simultaneous densification of the adjacent fat and infracentimetric ganglionic formations scattered throughout the mesentery were shown. Surgical biopsy revealed extensive storiform fibrosclerosis, with the presence of interstitial lymphoplasmocytic infiltrate and obliterative phlebitis (b); the plasma cells had mostly IgG expression, with IgG4:IgG ratio >40% (c), accounting for more than 30- 40 IgG4 plasma cells per field. The serum IgG4 level was 137mg/dL. A diagnosis of IgG4-related sclerosing mesenteritis was made, without other organ involvement. Prednisolone (0.6mg/kg/d) improved partially the abdominal pain, so steroid sparing strategy with off-label rituximab was associated. Due to its low prevalence, the understanding of this entity is scarce, and its diagnosis is challenging. Unlike other manifestations of IgG4-related disease, the intra-abdominal disease is identified in later stages, due to unspecific symptoms. This case aims to raise awareness about this condition as a differential diagnosis of abdominal pain.

Positioning Aeromonas Infection in Inflammatory Bowel Disease: A Retrospective Analysis.

Background and Aim: Aeromonas are Gram-negative rods known to cause a spectrum of diseases. Inflammatory bowel disease (IBD) is an idiopathic complex condition resulting from interaction of multiple factors. Aeromonas infection in association with IBD is still largely unknown. We aim to look for the significance of Aeromonas infection and for significant differences between IBD and non-IBD patients. Methods: A retrospective observational analysis was performed of all patients positive for Aeromonas in stool cultures, during a 10-year period, from a tertiary and university hospital. Results: Fifty patients were included, 56% male with a mean age of 42.1 years. Thirty-eight (76%) were non-IBD and 12 (24%) IBD patients. IBD patients were more frequently under immunosuppressors. Two patients were asymptomatic and 44% developed mild, 44% moderate, and 16.7% severe infection. The main strains isolated were Aeromonas hydrophila/caviae. Bacterial co-isolation was found in 4 non-IBD and histological findings of cytomegalovirus in 2 IBD patients. Non-IBD patients presented more frequently with fever and IBD patients with bloody diarrhea and abdominal pain. There was higher tendency for severe infection rate in IBD patients with higher antimicrobial therapy use. Steroids were exclusively used in the IBD group. From IBD, 4 patients had the diagnosis of ulcerative colitis and 9 of Crohn's disease with colonic involvement. Of these patients, 5 received IBD diagnosis after the acute episode of Aeromonas infection. Conclusions: Clinical presentation of Aeromonas infection differs between IBD and non-IBD patients. Non-IBD patients had milder severity of infection with less use of antibiotics. Aeromonas infection seems to greatly contribute to IBD manifestation.

Introdução: A etiologia da Doença Inflamatória Intestinal (DII) é complexa e resultante da interação de diversos fatores, nomeadamente microbiológicos. A infeção por Aeromonas caracteriza-se por um espectro alargado de manifestações clínicas. O papel da infeção por Aeromonas na DII não está caracterizado. Objetivos: Avaliar o significado da infeção por Aeromonas na DII e as diferenças com a infeção em doentes não-DII. Métodos: avaliação retrospetiva e observacional de todos os doentes com isolamento microbiológico de Aeromonas em amostras fecais num período de 10 anos, num hospital terciário. Resultados: foram avaliados 50 doentes, 56% do sexo masculino, com idade média de 42.1 anos. Doze (24%) com diagnóstico de DII e trinta e oito (76%) não-DII. Os doentes com DII encontravam-se mais frequentemente sob imunossupressão. Dois doentes foram assintomáticos, 44% desenvolveram doença ligeira, 44% moderada e 16.7% severa, havendo maior tendência para infeção severa nos DII. Os doentes não-DII apresentaram mais frequentemente febre e os DII diarreia sanguinolenta e dor abdominal. O uso de antimicrobianos foi superior no grupo DII e a utilização de corticoesteroides foi exclusiva nestes doentes. Isolamento concomitante de outros agentes microbiológicos ocorreu em 4 doentes não-DII e 2 com DII tinham histologia compatível com infeção por Citomegalovírus. Da população DII, 4 eram Colite Ulcerosa e 9 Doença de Crohn com envolvimento cólico. Destes, 5 receberam o diagnóstico após a infeção por Aeromonas. Conclusão: A apresentação clínica da infeção por Aeromonas foi distinta entre as populações DII e não-DII, sendo que os doentes DII apresentaram doença mais severa e maior utilização de antimicrobianos. A infeção na DII ocorreu essencialmente em doentes com envolvimento cólico.

Hemochromatosis and Xeroderma Pigmentosum: Two (Un)Suspicious Neighbors.

A 51-year-old woman, clinically diagnosed with Xeroderma pigmentosum (XP), showed abnormalities in liver enzymes, high ferritin and transferrin saturation levels, with ultrasonographic features of chronic liver disease, in addition to skin hyperpigmentation. Genetic testing confirmed the clinical hypothesis of hereditary hemochromatosis (HH). Due to the known proximity of HFE (6p22.2) and POLH (6p21.1) genes, accountable for HH and the XP-V variant, respectively, a genetic test was offered and a rare variant of the POLH gene was identified. We report the first confirmed case, to our knowledge, of a patient diagnosed both with XP and HH, in whom two mutated neighbor genes - POLH and HFE - were identified, possibly the result of genetic linkage.

Uma mulher de 51 anos, com antecedentes pessoais de Xeroderma pigmentosum (XP), apresentava, além de hiperpigmentação cutânea, alterações nas enzimas hepáticas, elevação da ferritina sérica e da saturação da transferrina, bem como alterações ecográficas compatíveis com doença hepática crónica. A realização de um teste genético permitiu confirmar a hipótese diagnóstica de Hemocromatose Hereditária (HH). Pela proximidade conhecida dos genes HFE (6p22.2) e POLH (6p21.1), responsáveis pela HH e pelo XP-V, respetivamente, foi realizado um teste genético que detetou um polimorfismo raro do gene POLH. Reportamos o primeiro caso de uma paciente diagnosticada com XP e HH, na qual foram identificados dois genes vizinhos mutados ­ POLH e HFE ­, possivelmente como resultado de ligação genética.

The Current Portrayal of Non-Variceal Upper Gastrointestinal Bleeding in a Portuguese Tertiary Center.

INTRODUCTION: Non-variceal upper gastrointestinal bleeding (NVUGIB) is an important healthcare problem whose epidemiology and outcomes have been changing throughout the years. The main goal of this study was to characterize the current demographics, etiologies, and risk factors of NVUGIB. METHODS: Analysis of clinical, endoscopic, and outcome data from patients who were admitted for NVUGIB between January 2016 and January 2019 in an emergency department of a tertiary hospital center. RESULTS: A total of 522 patients were included, with a median age of 71 years, mainly men, with multiple comorbidities. Most patients were directly admitted, while the others were transferred from other hospitals. Peptic ulcer disease was the most common cause of NVUGIB and it was followed by tumor bleeding. Esophagogastroduodenoscopy was performed within <12 h after hospital admission in 51.9%. In-hospital rebleeding occurred in 6.9% and overall mortality was 4.2%. Transferred patients had superior Glasgow-Blatchford score (GBS), required more blood transfusion, endoscopic and surgical interventions, and presented higher rebleeding rate, with similar mortality. Complete Rockall score (CRS) and GBS were predictors of endoscopic therapy. Surgery need was only related to CRS. Patients who rebled had superior pre-endoscopic Rockall score (RS), CRS, and GBS. Mortality was increased in patients with higher RS and CRS. DISCUSSION/CONCLUSION: Ageing and increasing comorbidities have not been related to worse outcomes in NVUGIB. These findings seem to be the consequence of the correct use of both diagnostic and therapeutic tools in an organized and widely accessible healthcare system.

Introdução: Hemorragia digestiva alta não-hipertensiva (HDANH) é um problema de saúde cuja epidemiologia e prognóstico têm-se alterado ao longo dos anos. O principal objetivo deste trabalho foi analisar a caracterização demográfica, etiologias e fatores de risco para HDANH. Métodos: Análise de dados clínicos, endoscópicos e prognóstico de doentes admitidos por HDANH entre janeiro/2016 e janeiro/2019 no serviço de urgência de um hospital terciário. Resultados: Foram incluídos 522 doentes, idade mediana de 71 anos, maioritariamente homens, com múltiplas comorbilidades. A maioria foi admitida diretamente, os restantes foram transferidos de outros hospitais. A doença-ulcerosa-péptica foi a causa mais frequente de HDANH, seguida pela etiologia neoplásica. Esofagogastroduodenoscopia foi realizada em menos de 12horas após admissão em 51.9%. Recidiva hemorrágica ocorreu em 6.9% e a taxa global de mortalidade foi 4.2%. Os doentes transferidos registaram um score Glasgow-Blatchford (GBS) superior, necessitaram mais frequentemente de transfusões, terapêutica endoscópica e cirúrgica, e apresentaram taxas superiores de recidiva hemorrágica, mas com mortalidade semelhante. O score Completo-Rockall (CRS) e o GBS foram preditores de terapêutica endoscópica. A necessidade de cirurgia esteve associada ao CRS. Os doentes com recidiva hemorrágica tiverem superiores score Rockall pre-endoscópico (RS), CRS e GBS. Mortalidade superior esteve associada a RS e CRS mais elevados. Discussão/Conclusão: O envelhecimento e o aumento das comorbilidades não se associaram a piores outcomes na HDANH. Estes achados parecem ser consequência do uso adequado de ferramentas diagnósticas e terapêuticas num sistema de saúde organizado e amplamente acessível.

Acute variceal bleeding and out-of-hours endoscopy: Evaluation of an emergency care setting according to Baveno VI guidelines adherence.

BACKGROUND: The extent to which patients with acute variceal bleeding (AVB) receive recommended care is largely unknown. AIM: to evaluate the adherence of the 4 major Baveno VI recommendations [vasoactive agents, prophylactic antibiotic, esophagogastroduodenoscopy (EGD) within 12 hours, endoscopic variceal ligation (EVL)] as a marker of quality of an emergency model. METHODS: Retrospective evaluation of AVB admissions to a tertiary centre in which endoscopy was available 24hours-a-day, with a regional out-of-hours service at night (the furthest hospital is 200Km away). Patients were divided in directly admitted or transferred from other centres. RESULTS: 210 AVB patients were included; 101 (48.1%) were directly admitted. The majority of patients were submitted to vasoactive agents (85.7%) and prophylactic antibiotics (79%) before EGD. In 178 patients (84.8%) endoscopy was performed within 12h and EVL was the procedure of choice in 116 (74.8%) (only oesophageal varices). No significant differences were observed between directly admitted and transferred patients in adherence rates. Overall rebleeding rate was 8.6%, in-hospital mortality 11.4% and 6-week mortality 20%. CONCLUSION: Adherence to quality metrics was high which might have played a vital role for reported outcomes. These results suggest that this model of care, provides accessibility and equity in access to urgent endoscopy.

Impact of Liver Test Abnormalities and Chronic Liver Disease on the Clinical Outcomes of Patients Hospitalized with COVID-19.

BACKGROUND AND AIMS: The impact of SARS-CoV-2 infection on the liver and the possibility of chronic liver disease (CLD) as a risk factor for COVID-19 severity is not fully understood. Our goal was to describe clinical outcomes of COVID-19 inpatients regarding the presence of abnormal liver tests and CLD. METHODS: A retrospective analysis of patients with SARS-CoV-2 infection, hospitalized in a tertiary center in Portugal, was performed. Studied outcomes were disease and hospitalization length, COVID-19 severity, admission to intensive care unit (ICU) and mortality, analyzed by the presence of abnormal liver tests and CLD. RESULTS: We included 317 inpatients with a mean age of 70.4 years, 50.5% males. COVID-19 severity was moderate to severe in 57.4% and critical in 12.9%. The mean disease length was 37.8 days, the median hospitalization duration 10.0 days and overall mortality 22.8%. At admission, 50.3% showed abnormal liver tests, and 41.5% showed elevated aminotransferase levels, from which 75.4% were mild. Elevated aminotransferase levels at admission were associated with COVID-19 severity (78.7 vs. 63.3%, p = 0.01), ICU admission (13.1 vs. 5.92%, p = 0.034) and increased mortality (25.8 vs. 13.3%, p = 0.007). However, in a subgroup analysis, only aspartate transaminase (AST) was associated with these worse outcomes. Alkaline phosphatase was elevated in 11.4% of the patients and was associated with critical COVID-19 (21.1 vs. 9.92%, p = 0.044) and mortality (20.4 vs. 9.52%, p = 0.025), while 24.6% of the patients showed elevated γ-glutamyl transferase, which was associated with ICU admission (42.3 vs. 22.8%, p = 0.028). Fourteen patients had baseline CLD (4.42%), 3 with liver cirrhosis. Alcohol (n = 6) and nonalcoholic fatty liver disease (n = 6) were the most frequent etiologies. CLD patients had critical COVID-19 in 21.4% (p = 0.237), mean disease length of 36.6 days (p = 0.291), median hospitalization duration of 11.5 days (p = 0.447) and a mortality rate of 28.6% (p = 0.595), which increased to 66.7% among cirrhotic patients (p = 0.176). CONCLUSIONS: Liver test abnormalities in COVID-19 patients were frequent but most commonly mild. AST, but not alanine transaminase, was associated with worse clinical outcomes, such as COVID-19 severity and mortality, probably indicating these outcomes were independent of liver injury. A low prevalence of CLD was seen, and a clear impact on COVID-19 outcomes was not seen.

Long-Term Follow-Up of a Portuguese Single-Centre Cohort of Persons with Haemophilia and Hepatitis C Virus Infection.

INTRODUCTION: Persons with haemophilia (PWH) used to represent a population with a high prevalence of hepatitis C virus (HCV) infection due to the use of contaminated blood products. Although the goals of antiviral therapy are the same as the general population, long real-life follow-up data regarding their outcomes are still scarce. Our aim was to report the outcomes of HCV infection and the results of antiviral therapy in PWH. METHODS: A retrospective analysis was performed in a single-centre cohort of PWH with positive HCV antibody. Outcomes registered were rate of spontaneous clearance of HCV, sustained virologic response (SVR) achievement, development of end-stage liver disease, and all-cause and liver-related mortality. RESULTS: Out of 131 PWH, 73 (55.7%) had positive HCV antibody. During a median follow-up time of 22 years, 46 patients (63.9%) developed chronic hepatitis C, of which 16 (34.8%) developed cirrhosis. Treatment was pursued in 34 PWH. Most (n = 32) were first treated with interferon (IFN)-based regimens with SVR rates of 40.6%. Direct-acting antivirals were used in 14 IFN-experienced and 2 naïve patients, with an overall SVR rate of 100%. Overall, 17 patients (23.3%) died during the follow-up, only 4 related to liver disease. Of these, none had achieved SVR. CONCLUSIONS: We describe the outcomes of a cohort of Portuguese PWH and hepatitis C exposure after two decades of follow-up, with a lower mortality than previously described. Our response rates to HCV treatment were comparable to those in the general population and stress the importance of early treatment.

INTRODUÇÃO: A população de doentes com hemofilia (DCH) representa uma população com alta prevalência de infeção pelo virus da hepatite C (VHC), atendendo à utilização passada de derivados sanguíneos contaminados. Apesar de os objetivos terapêuticos nesta população serem semelhantes aos da população geral, estudos de vida real com follow-up de longa data são ainda escassos. O nosso objetivo consistiu em avaliar os outcomes infeção VHC, bem como, os resultados da terapéutica antivírica nos DCH. MÉTODOS: Foi avaliada retrospetivamente uma coorte unicêntrica de DCH com positividade para anti-VHC. Os outcomes registados foram a ocorrência de clearance espontêneo, resposta virológica sustentada (RVS), desenvolvimento de doença hepática terminal e mortalidade. RESULTADOS: De 131 DCH, 73 (55.7%) apresentavam positividade para o anticorpo VHC. Durante um follow-up médio de 22 anos, 46 doentes (63.9%) desenvolveram hepatite crónica C, 16 (34.8%) dos quais com desenvolvimento de cirrose. Trinta e quatro DCH foram tratados, a maioria (n = 32) exposta previamente a regimes baseados no interferão (IFN) com RVS de 40.6%. Antivíricos de ação direta foram utilizados em 14 doentes experimentados a IFN e 2 naïves com uma taxa de RVS geral de 100%. Morte foi observada em 17 doentes (23.3%), apenas 4 relacionadas à doença hepática. Destes nenhum tinha atingido RVS. CONCLUSÕES: Descrevemos os outcomes de uma coorte portuguesa de DCH e VHC após duas décadas de follow-up, mostrando uma mortalidade inferior à previamente descrita. As taxas de RVS mostradas foram comparáveis com as da população geral salientando a importancia do tratamento precoce.

Vedolizumab-associated psoriasis: until where does gut selectivity go?

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Long-Term Follow-Up of Advanced Liver Disease after Sustained Virological Response to Treatment of Hepatitis C with Direct-Acting Antivirals: Outcomes from a Real-World Portuguese Cohort.

BACKGROUND: Direct-acting antivirals (DAA) have revolutionized hepatitis C treatment, with high sustained virological response (SVR) rates reported, even in historically difficult-to-treat groups. SVR is associated with a decreased risk of hepatocellular carcinoma (HCC), need for transplantation, and overall and liver-related mortality. Data from real-life cohorts on the medium- to long-term outcomes of patients with advanced liver disease and DAA-induced SVR are still missing. OBJECTIVES: To report and analyze the long-term outcomes of DAA-induced SVR in a real-life cohort of patients with advanced liver disease. METHOD: In this retrospective, longitudinal, single-center study, we collected data from patients with chronic hepatitis C infection and advanced liver disease (cirrhosis or advanced fibrosis) that had initiated DAA treatment between February 2015 and January 2017. RESULTS: A total of 237 patients were included. A treatment completion rate of 98.7% and an SVR rate of 97.8% (intention to treat: 96.6%) were found. Of the 229 patients with SVR, 67.2% were cirrhotic (64.2% Child-Pugh class A; 3.1% Child-Pugh class B) and 32.8% had stage F3 fibrosis, with an average follow-up of 28 months. The overall mortality rate was 19/1,000 person-years and the liver-related mortality rate was 9.5/1,000 person-years. The hepatic decompensation incidence rate was 25/1,000 person-years and the HCC incidence rate was 11.6/1,000 person-years. There was a sustained increase in serum platelet values during up to 2 years of follow-up. A history of pretreatment decompensation and baseline platelet and albumin values were significantly associated with the occurrence of adverse liver events after the end of treatment. CONCLUSIONS: A DAA-induced SVR remains durable and is associated with an excellent clinical prognosis in patients with compensated advanced liver disease and with improvement or disease stabilization in decompensated patients. SVR is associated with a low risk of - yet does not prevent - HCC occurrence or disease progression, especially in the presence of other causes of liver injury. It is recommended that these patients be kept under surveillance.

Resumo. INTRODUÇÃO: Os antivíricos de ação direta (AAD) revolucionaram o tratamento da hepatite C ao atingirem elevadas taxas de resposta virológica sustentada (RVS), mesmo em grupos historicamente difíceis de tratar. A RVS associa-se a uma diminuição do risco de carcinoma hepatocelular (CHC), necessidade de transplantação e mortalidade, global e de causa hepática. São ainda insuficientes de coortes reais na literatura dados que permitam avaliar a extensão dos benefícios clínicos a médio-longo prazo do atingimento de uma RVS com os AAD. OBJETIVOS: Reportar e analisar o impacto a longo prazo da RVS numa coorte real de doentes com doença hepática avançada, tratados com AAD. MÉTODOS: Estudo unicêntrico, retrospetivo, longitudinal com inclusão de doentes com hepatite C crónica com cirrose ou fibrose avançada, que iniciaram tratamento com AAD de fevereiro de 2015 a janeiro de 2017. RESULTADOS: Foram incluídos 237 doentes. Verificou-se uma taxa de retenção no tratamento de 98.7% com uma taxa de RVS de 97.8% (intention to treat: 96.6%). Dos 229 doentes curados, 67.2% eram cirróticos (64.2%Child-Pugh A, 3.1 % Child-Pugh B) e 32.8% F3, com um seguimento médio de 28 meses. A taxa de mortalidade global foi de 19/1,000 pessoas-ano e de mortalidade associada à doença hepática de 9.5/1,000 pessoas-ano. A incidência de eventos de descompensação hepática foi de 25/1,000 pessoas-ano e a de CHC foi de 11.6/1,000 pessoas-ano. Verificou-se um aumento sustentado dos valores séricos de plaquetas até 2 anos de seguimento. A história de eventos de descompensação hepática, concentração de plaquetas e albumina prétratamento encontrou-se significativamente associada a eventos adversos hepáticos durante o seguimento. CONCLUSÕES: A cura virológica após tratamento com AAD é sustentada no tempo, encontrando-se associada a um excelente prognóstico clínico em doentes com doença hepática avançada compensada, e a uma melhoria ou estabilização da doença em doentes descompensados. O atingimento de RVS associa-se a um baixo risco de CHC, não o eliminando, e de progressão da doença, sobretodo perante a presença de outros cofatores de agressão hepática, recomendando-se a manutenção do seguimento destes doentes.

Vedolizumab-associated psoriasis: until where does gut selectivity go?

Inflammatory Bowel Disease and Psoriasis are chronic inflammatory diseases that share common genotype, clinical course, and immunological features, although its relationship is still unclear. We report a 34-year-old woman with ileal Crohn's disease diagnosed 14 years ago, with the development of extensive, exudative scalp lesions after adalimumab therapy. Biopsies from skin lesions were compatible with vulgar psoriasis. The patient reports no personal or family history of psoriasis. Due to persistence and further worsening of skin lesions, paradoxical etiology to adalimumab was presumed and the drug was stopped with complete resolution of skin lesions and intestinal disease in remission under methotrexate. Due to pregnancy-planification methotrexate was stopped and, 8 months-after, systemic steroid-therapy was introduced due to moderate-to-severe intestinal flare. Vedolizumab was started and at the second infusion patient reported hair loss with no other complaints. Twelve months after vedolizumab initiation the patient reported reappearance of the extensive scalp and peri-fistula psoriatic lesions. Topical therapy was started but unsuccessfully and given the progressive worsening of the lesions, vedolizumab was suspended, with skin improvement seen 1 month after discontinuation. There are few case-reports of vedolizumab acting as a trigger to some dermatological conditions in IBD-patients, including psoriasis. The molecular mechanism behind it isn't fully understood. We present and discuss, to our knowledge, the first case in the literature of psoriasis triggered by vedolizumab in Crohn's disease.

[Use of Anterolateral Thigh Free Flap in the Treatment of a Sternal Keloid]. / Retalho Livre Anterolateral da Coxa para Tratamento de Quelóide Esternal.

Hypertrophic and keloid scars represent hyperproliferative disorders that can have a significant impact on patients' lives. The authors present the case of a 53 years-old male with a sternal keloid after excision of a sebaceous cyst and multiple sessions of steroid infiltration, with worsening of the lesion. The patient underwent complete excision of the scar and reconstruction with an anterolateral thigh flap - ALT. The postoperative period was uneventful, with no signs of relapse. Keloid scar treatment in sternal area implies a reconstruction with no tension, in order to avoid relapse. Treatment of this type of scars is complex and a challenge to the plastic surgeon. In this case, a microvascular tissue transfer was used to reconstruct the large defect that ultimately resulted after scar excision, in a tension-free manner.

As cicatrizes hipertróficas e quelóides representam distúrbios cicatriciais hiperproliferativos que podem ter um impacto significativo na vida dos doentes. Os autores apresentam o caso de um doente de 53 anos, com uma cicatriz quelóide na região esternal após exérese de quisto sebáceo e múltiplas sessões de infiltração de corticóide, com um agravamento marcado da lesão. O doente foi submetido a exérese do quelóide e reconstrução do defeito com retalho livre fasciocutâneo anterolateral da coxa (anterolateral thigh flap ­ ALT). O pós-operatório imediato e tardio decorreu sem intercorrências, sem sinais de recidiva. O tratamento de quelóides esternais passa, inevitavelmente, por diminuir a tensão na região operada, de forma a evitar a recidiva e eventual agravamento da lesão. O tratamento deste tipo de cicatrizes é complexo, tornando-se um verdadeiro desafio para o cirurgião plástico. No caso clínico apresentado, dadas as dimensões e localização da cicatriz, a sua excisão provocou um defeito extenso, sendo necessária a transferência microcirúrgica de tecidos para cobertura completa, minimizando a tensão na região esternal.

Contemporary Concepts of Primary Dynamic Facial Nerve Reconstruction in the Oncologic Patient.

Transection of the facial nerve and its branches during extensive ablative procedures in the oncologic patient causes loss of control of facial mimetic muscles with severe functional and aesthetic sequelae. In such patients with advanced tumorous disease, copious comorbidities, and poor prognosis, rehabilitation of the facial nerve has long been considered of secondary priority. However, recent advances in primary facial nerve reconstruction after extensive resection demonstrated encouraging results focusing on rapid and reliable restoration of facial functions. The authors summarize 3 innovative approaches of primary dynamic facial nerve reconstruction by using vascularized nerve grafts, dual innervation concepts, and intra-facial nerve transfers.

Versatilidad del colgajo famm para la cobertura de defectos intraorales / Versatility of the famm flap in intraoral reconstruction / Versatilidade do retalho FAMM na cobertura de defeitos intra-orais

Introducción y Objetivo: El colgajo FAMM (colgajo músculo-mucoso de arteria facial) descrito en 1992 por Pribaz y col, es un colgajo intraoral basado en la arteria facial, compuesto por mucosa oral, submucosa, músculo bucinador, arteria facial y por el plexo venoso correspondiente y puede ser de base inferior (flujo anterógrado) o superior (flujo retrógrado). Es un colgajo versátil que se puede usar en la reconstrucción de defectos de múltiples localizaciones (paladar, lengua o suelo de boca). Con este trabajo pretendemos demostrar su utilidad en la reconstrucción de diferentes defectos intraorales. Material y Método: Presentamos 3 casos en lo que empleamos el colgajo FAMM para reconstrucción intraoral: un paciente con anquiloglosia cicatricial secuela de carcinoma de suelo de boca, un paciente con fístula de paladar secuela de resección tumoral, y un paciente con exposición intraoral de arco mandibular por osteonecrosis secundaria a bifosfonatos. Resultados: Todos los colgajos sobrevivieron al 100% y permitieron una cobertura estable y duradera, con ausencia de complicaciones mayores. Conclusiones: El colgajo FAMM permite la reconstrucción de defectos intraorales y periorales con tejido bien vascularizado y de idénticas características a las de la zona a reconstruir, con baja morbilidad de la zona donante, lo que lo convierte en una excelente opción reconstructiva para defectos de esta región anatómica

Background and Objective: The facial artery musculo-mucosal (FAMM) flap, first described by Pribaz et al. in 1992, is an intraoral flap based on the facial artery. It is composed of mucosa, submucosa, buccinator muscle and the facial artery along with its venous plexus. The design of the flap can be inferiorly-based and rely on antegrade blood flow or superiorly-based with retrograde flow. The FAMM flap is a versatile flap that can be used for the reconstruction of defects of multiple locations (palate, lips, tongue, and floor of the mouth). The purpose of this study is to demonstrate the utility of the FAMM flap in the reconstruction of different intraoral defects. Methods: In this article the authors present 3 cases in which the FAMM flap was used for intraoral reconstruction: one patient with a history of ankyloglossia sequelae of a squamous cell carcinoma of the floor of the mouth; one patient with a palatal fistula sequelae of tumor excision; and one patient with a biphosphonate-related osteonecrosis of the mandible. Results: All flaps survived and provided a stable and reliable coverage of the defect. There were no major complications. Conclusions: The FAMM flap is a well vascularized flap that replaces like with like tissue. Because of its low morbidity, low rate of complications and reliable results, the FAMM flap is an excellent option for reconstruction of small to moderate intra-oral defects

Introdução e Objetivo: O retalho FAMM (facial artery musculo-mucosal flap), descrito em 1992 por Pribaz et al., é um retalho intra-oral baseado na artéria facial. É composto por mucosa oral, submucosa, músculo bucinador, artéria facial e pelo plexo venoso correspondente, podendo basear-se inferior (fluxo anterógrado) ou superiormente (fluxo retrógrado). É um retalho versátil que pode ser utilizado nareconstrução de defeitos em múltiplas localizações (palato, lábio, língua, pavimento da boca). Com este trabalho pretende-se demonstrar a utilidade do retalho FAMM na reconstrução de diferentes defeitos intra-orais. Material e Métodos: Os autores apresentam 3 casos em que se utilizou o retalho FAMM para reconstrução intra-oral: um doente com anquiloglossia cicatricial sequelar de carcinoma do pavimento da boca; uma doente com uma fístula do palato sequela de excisão tumoral; e um doente com exposição intra-oral do arco mandibular anterior por osteonecrose secundária a bifosfonatos. Resultados: Todos os retalhos sobreviveram a 100% e permitiram uma cobertura estável e duradoura, na ausência de complicações major. Conclusão: O retalho FAMM permite a reconstrução de defeitos intra e peri-orais com tecido bem vascularizado e de características idênticas à zona a reconstruir, com baixa morbilidade da zona dadora, o que o torna uma excelente opção reconstrutiva para defeitos desta região anatómica

Otimização do dimensionamento em sistemas de bombeamento fotovoltaico: validação de modelo em sistema piloto na comunidade rural de Rio Belo, Orleans (SC) / Sizing optimization in Solar Photovoltaic Water Pumping System: model validation in a pilot unit located in the rural community of Rio Belo, Orleans/SC, Brazil

RESUMO A gestão dos recursos hídricos e energéticos é o principal desafio que a sociedade contemporânea enfrenta atualmente. Água e energia são fatores fundamentais para o desenvolvimento socioeconômico das comunidades, principalmente aquelas situadas em locais remotos, e, nesse cenário, a falta de energia é o aspecto mais preocupante. Os sistemas de bombeamento fotovoltaico apresentam vantagens para a inserção em comunidades isoladas, como fácil instalação e pouca manutenção durante o ciclo de vida, porém o dimensionamento inadequado pode gerar gastos desnecessários ou comprometer o abastecimento de água. Simular o desempenho favorece a concepção de sistemas e permite alcançar a otimização técnica e econômica em projetos da referida tecnologia. O estudo propõe um modelo matemático de simulação e a utilização do generalized reduced gradient (GRG) e de dados regionais de radiação solar, de consumo de água, de produtividade de poços e de capacidade do sistema de bombeamento para obter a referida otimização. A validação do respectivo modelo foi realizada em um sistema piloto, localizado em uma comunidade rural no município de Orleans, no Estado de Santa Catarina. A localidade apresenta uma das menores médias de radiação anual no país, aproximadamente 4,5 kWh.m-2/dia. A simulação efetuada nas condições naturais do sistema piloto mostrou resultados bem próximos do comportamento monitorado, evidenciando, assim, a eficiência do modelo. O uso da ferramenta auxilia no processo de tomada de decisão quanto à concepção de projetos, além de beneficiar as comunidades com acesso à água e à energia, trazendo benefícios em todas as esferas: social, ambiental e econômica.

ABSTRACT The management of water and energy resources are the main challenges that contemporary society faces nowadays. Water and energy are fundamental factors for socio-economic development of the communities, especially those in remote locations, and in this case the lack of energy is the most worrying aspect. Solar photovoltaic pumping systems have advantages for insertion in isolated communities, such as easy installation and low maintenance during the life cycle, but inappropriate sizing can create unnecessary costs or affect the water supply. Simulating performance favors the system's sizing and allows achieving technical and economic optimization of these technology projects. This study proposes a mathematical model of simulation, use of the Generalized Reduced Gradient (GRG), solar radiation regional data, and water consumption, wells' productivity and pumping system capacity to obtain this optimization. The model was validated in a pilot system, located in a rural community in the city of Orleans, State of Santa Catarina, Brazil. The place has one of the lowest average annual radiation in the country, approximately 4.5 kWh / m2.day. The simulation performed in the natural pilot system conditions presented results very close to the monitored behavior, thus demonstrating its efficiency. Using this tool assists in the decision-making process in designing projects and benefits the communities with access to water and energy, bringing benefits in all spheres: social, environmental and economic.

Detailed characterization of incretin cell distribution along the human small intestine.

BACKGROUND: Incretin hormones, glucose-dependent insulinotropic polypeptide (GIP) and glucagon-like peptide 1 (GLP-1), are physiologic stimulants of insulin release that have been implicated in diabetes remission after bariatric surgery. The detailed distribution of incretin cells along the human small gut, so far unknown, is of utmost importance for the understanding of the metabolic changes observed after bariatric surgery because diabetes remission rate varies according to the type of anatomic rearrangement. OBJECTIVE: To characterize the distribution of incretin producing cells along the human jejunum-ileum. SETTING: Academic public institution. METHODS: Small intestines (n = 30) from autopsies were sampled every 20 cm along their entire length and tissue microarrays were constructed. The percentage of immunohistochemistry-stained cell areas for GLP-1, GIP, and chromogranin A at each segment length was quantified using a computer-aided analysis tool. RESULTS: The percentage of stained area for GLP-1 immunoreactive cells was found to be significantly higher from 200 cm from Treitz ligament onward compared with the first 80 cm of the small intestine, whereas GIP immunoreactive cells were predominant expressed in the first 80 cm. In contrast, chromogranin A expression was constant along the entire jejunum-ileum. CONCLUSION: The uneven distribution of GLP-1-expressing cells, with a higher density from 200 cm of the jejunum-ileum, could contribute to explain the improvement of glycemic profile of diabetic patients observed after anatomic rearrangement of the intestinal tract, in particular when subjected to gastric bypass with longer biliopancreatic limbs.

Manifestações neuropsiquiátricas da Síndrome de Fahr: relato de caso / Neuropsychiatric manifestations of Fahr's Syndrome: a case-report

As calcificações cerebrais são alterações relativamente comuns, podendo estar presentes em diversas condições clínicas. A Síndrome de Fahr é uma destas condições. Relatamos o caso de uma paciente com alterações do comportamento, do humor, desordens dos movimentos e crises convulsivas. Foram encontradas alterações tomográficas compatíveis com a Síndrome de Fahr e achados laboratoriais típicos do hipoparatireoidismo.

Brain calcifications are relatively common and may be present in various clinical conditions. Fahr's syndrome is one of those conditions. We report a patient with abnormal behavior, changes of mood, movement disorders and seizures. CT changes consistent with the pattern described for Fahr's Syndrome and laboratory findings typical of hypoparathyroidism were found.